Genetic Variant IQGAP2:c.1522-4004T>C (chr5-76623406-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006633.5(IQGAP2):c.1522-4004T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000869 in 644,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

IQGAP2
NM_006633.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.466

Publications

1 publications found

Variant links:

Genes affected

IQGAP2 (HGNC:6111): (IQ motif containing GTPase activating protein 2) This gene encodes a member of the IQGAP family. The encoded protein contains three IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. This protein interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. It also acts as a tumor suppressor and has been found to play a role in regulating innate antiviral responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

IQGAP2 links:

F2RL2 (HGNC:3539): (coagulation factor II thrombin receptor like 2) This gene encodes a member of the protease-activated receptor (PAR) family which is a subfamily of the seven transmembrane G protein-coupled cell surface receptor family. The encoded protein acts as a cofactor in the thrombin-mediated cleavage and activation of the protease-activated receptor family member PAR4. The encoded protein plays an essential role in hemostasis and thrombosis. Alternate splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Feb 2012]

F2RL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQGAP2	NM_006633.5 link	c.1522-4004T>C		intron_variant	Intron 13 of 35	ENST00000274364.11	NP_006624.3	Q13576-1B7Z7U6Q59HA3
F2RL2	NM_004101.4 link	c.-176A>G		upstream_gene_variant		ENST00000296641.5	NP_004092.1	O00254-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11 link	c.1522-4004T>C		intron_variant	Intron 13 of 35	1	NM_006633.5	ENSP00000274364.6		Q13576-1
F2RL2	ENST00000296641.5 link	c.-176A>G		upstream_gene_variant		1	NM_004101.4	ENSP00000296641.3		O00254-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000995

AC:

AN:

492348

Hom.:

Cov.:

AF XY:

0.0000850

AC XY:

AN XY:

258916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13144

American (AMR)

AF:

0.00

AC:

AN:

18690

Ashkenazi Jewish (ASJ)

AF:

0.000716

AC:

AN:

13964

East Asian (EAS)

AF:

0.00109

AC:

AN:

31252

South Asian (SAS)

AF:

0.0000217

AC:

AN:

46114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2108

European-Non Finnish (NFE)

AF:

0.00000653

AC:

AN:

306424

Other (OTH)

AF:

0.0000733

AC:

AN:

27270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000459

AC:

AN:

152378

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41602

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000793

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.5

(source)

DANN

Benign

0.70

PhyloP100

0.47

PromoterAI

0.18

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over